Vaccination vial and needle. ©shuttershock
Vaccinations (vaccines) have been a game changer in the medical world and human health. They’ve helped protect us from measles and mumps, polio, and most recently COVID-19. They’ve even eradicated smallpox, one of the deadliest diseases in human history. Can they do something similar for cancer?
Many vaccines are made from weakened or harmless versions of the virus or bacteria that they’re designed to stop. They teach our immune system how to fight off illness without actually making us ill.
Let’s take COVID-19 as an example. COVID vaccines train the body to make specific anti-COVID antibodies, blood proteins that the immune system uses to recognise and attack infections. This means that, if you come into contact with COVID-19 at a later date the immune system knows how to fight it.
So where does cancer come into this? Well, the immune system in our bodies is one of our best defences against cancer. But cancer cells can find ways to escape it, and when they do that’s when it can develop and spread. Sometimes, the immune system needs a boost. Researchers believe cancer vaccines could be an answer.
It falls under an umbrella of treatments called cancer immunotherapy, where the immune system is utilised to reduce the size of tumours and treat cancer.
A history of vaccines and cancer
The concept of using vaccines for cancer isn’t completely new. Over the years scientists have shown associations between certain viruses and increased risk of some cancer types. For example, HPV being a cause of cervical cancer.
HPV was first linked to cervical cancer in the 1980s. It is an extremely common virus. Around 8 out of 10 people will be infected with HPV at some point in their lives. Not all cases of HPV will end up causing cervical cancer, but it can increase the risk.
The HPV vaccine is given out in a nationwide programme. Originally, it vaccinated adolescent girls against 2 strains of HPV – HPV 16 and 18. These strains are connected to around 7 in 10 cervical cancer cases. Now, the vaccine extends its protection against 9 strains of HPV and is offered to all children aged 11-13. For those who missed out on receiving it, there is a catch up programme up to the age of 25.
Results from a landmark study in 2021 showed the vaccine was effective in reducing cervical cancer risk. In fact, the vaccine was shown to reduce cervical cancer rates by almost 90% in women in their 20s who were offered it at age 12 to 13.
Similarly, Hepatitis B has been linked to liver cancer, increasing risk by 15-25%. The chance of getting the virus is low in the UK, but if you’re travelling to a country where it is more common, you can get vaccinated.
However, these are preventative examples – where vaccines are being used to prevent a virus, which in turn reduces cancer risk.
Developing vaccines against cancer itself is something different. The idea behind these vaccines is that they will be used to treat cancer, rather than preventing it.
How do cancer vaccines work?
In the same way traditional vaccines use part of the virus to prevent disease, cancer vaccines use harmless proteins from the surface of cancer cells known as antigens.
When these antigens are introduced into the body, they should stimulate the immune system to produce antibodies against them, giving it the tools to kill cancer cells.
But this isn’t straightforward. Tumours are different for every individual, and they have different antigens. So, there can’t be one universal vaccine for cancer – different vaccines will need to be created for different tumour types.
That’s not the only problem. A lot of the antigens made by tumours can look like the body’s own antigens. Using these in a vaccine could cause the immune system to target healthy cells, which can have dangerous side effects.
Thankfully, researchers have been able to identify a range of tumour-specific antigens, which aren’t found on healthy cells, and tumour-associated antigens, which are present on some normal cells. These antigens are useful markers to help the immune system target cancer cells while leaving healthy parts of the body alone.
The next step is delivering these antigens into the body. To do that, scientists are trying out lots of different cancer vaccine technologies.
Types of cancer vaccine
Protein or peptide vaccines
These vaccines are made from special proteins in cancer cells, or from small pieces of protein (peptides). They aim to stimulate the immune system to attack the cancer. Scientists have worked out the genetic codes of many cancer cell proteins, so they can make them in the lab in large quantities.
DNA and RNA vaccines
Bits of genetic material (DNA or RNA) that are usually found in cancer cells are used for these vaccines. They’re injected into the body, delivering information to the body’s cells and instructing them to make proteins that begin an immune response.
Whole cell vaccines
A whole cell vaccine uses the whole cancer cell, not just a specific cell antigen, to make the vaccine. The cancer cells are changed in the lab to make them easier for the immune system to find.
For these vaccines, scientists use the patient’s own cancer cells, another person’s cancer cells or cancer cells that were grown in the laboratory.
Dendritic cell vaccines
Dendritic cells help the immune system recognise and attack abnormal cells, such as cancer cells. To make the vaccine, scientists grow dendritic cells, a type of immune cell, alongside cancer cells in the lab. The vaccine then stimulates the immune system to attack the cancer.
Scientists can change viruses in the laboratory and use them as a type of carrier to deliver cancer antigens into the body. They change the viruses so that they cannot cause serious disease. The altered virus is called a viral vector.
Some vaccines use a viral vector to deliver cancer antigens into the body. The immune system responds to the viral vector. This then helps the immune system to recognise and respond to the cancer antigen.
You can learn more about the different types of cancer vaccine on our About Cancer pages.
How far have we come?
Some types of cancer vaccines are showing more promise than others. Dendritic cell vaccines are already making a real difference to people with cancer. They use a type of immune cell, called dendritic cells to kick-start the immune system.
These dendritic cells are loaded with cancer antigens and display them on their surface like a badge. This ‘badge’ guides other immune molecules, called T-cells, to target and attack other cells with these antigens.
Sipuleucel-T (also known as Provenge), was developed for treating prostate cancer and became the first dendritic cell vaccine approved by the Food and Drug Administration in the US in 2010. A clinical trial showed that the vaccine reduced the risk of death by 22.5%.
Dendritic cell vaccines have the advantage of being very target specific. They’re made using the patients’ own cancer cells, allowing the vaccine to be well tolerated with little to no side effects. But the process is costly and slow.
The main issue of this type of treatment, is that cancer causes a suppressed immune system. This means that cancer can actively stop the immune system from attacking it.
T-cells have proteins, called checkpoints, which can turn the immune system off when it is no longer needed. But cancer cells interact with checkpoints and tricks the immune system to turn off, preventing an attack.
Immunotherapy drugs called checkpoint inhibitors turn the T-cells back on and attack cancer cells. While this type of immunotherapy is relatively successful, it doesn’t work for everyone.
But progress in the field of immunology has significantly increased, thanks to new technologies.
Learning from COVID-19
The COVID-19 pandemic has accelerated the production of vaccines, specifically mRNA vaccines. Their international success has influenced the direction of research when it comes to cancer vaccines.
Messenger RNA (mRNA) is a genetic material that copies instructions from our DNA and uses them to make proteins that carry out different functions in the body. Unlike traditional vaccines, which use dead or weakened viruses, these vaccines use mRNA with the instructions for making a cancer antigen. When it’s injected, this mRNA guides some of our cells to make harmless antigens, stimulating the immune response.
Part of the allure of mRNA vaccines is their speed and efficiency. To make an inactivated virus vaccine, scientists need to isolate the virus, grow it, inactivate it and formulate it. With mRNA they only need the right sequence of genetic instructions.
Vaccines that use mRNA can be more specific. Scientists can use mRNA technology to identify all the tumour’s unique genetic sequences or mutations. That helps the immune system spot and target only cancer cells and not healthy ones. Also, side effects in the body are minimal, making mRNA vaccines an attractive alternative to chemotherapy.
mRNA vaccines are one of the most exciting research developments to come out of the pandemic, and there are strong hints that they could become powerful treatment options for cancer.
Dr Iain Foulkes, Executive Director of Research and Innovation at Cancer Research UK
It took a long time for mRNA to start being used in the development of treatments. It was discovered in 1961, but took another 20 years for scientists to replicate it in the laboratory. MRNA is also notoriously fragile, so delivery into the body was a huge challenge until 2008, when researchers discovered how to stabilise it in a vaccine.
Even once these biological roadblocks had been cleared, it took the pressure of a pandemic to push mRNA into the mainstream. Before then, it had only been used in clinical trials.
The next steps
Earlier this year, the UK government announced it was partnering with BioNTech, who contributed to the development of the Pfizer COVID-19 vaccine. Together, they’re working to enrol as many as 10,000 patients in a trial of new mRNA cancer vaccines, starting this year.
“Our goal is to accelerate the development of immunotherapies and vaccines using technologies we have been researching for over 20 years,” says Professor Ugur Sahin BioNTech’s co-founder and chief executive.
“The collaboration will cover various cancer types and infectious diseases affecting collectively hundreds of millions of people worldwide.”
This partnership will give many early and late-stage cancer patients early access to explore alternative personalised therapies, including cancer vaccines. Part of their plan involves setting up a UK Research and Development hub in Cambridge by the end of 2023.
So, where are we?
When making cancer vaccines, researchers face a lot of challenges.
Some have already been overcome. Thanks to the discovery of tumour-specific antigens, we already know how to target tumours. But there are also some challenges which are unavoidable, like the length of time it takes to trial and test a vaccine and the need to develop specific vaccines to target different types of tumours.
However, cancer vaccines have made significant developments recently. The use of mRNA has transformed the typical vaccine timeline to one that is faster and more effective. And this new partnership will speed up the development even more, with more vaccines, more trials and more participants.
A few decades ago, cancer vaccines were science fiction. Now they’re becoming a reality.
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